Contrast-Induced Nephrotoxicity: Possible Synergistic Effect of Stress Hyperglycemia

Abstract

Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity. Dog kidney cells were incubated with 5- and 30-mmol/L glucose solutions and no glucose and then exposed for 2 hours to three types of contrast media-high osmolar (370 mg I/mL), low osmolar (300 mg I/mL), and isoosmolar (320 mg I/mL)-and a mannitol control solution. In an identical experiment, each group of cells was pretreated with an antioxidant-N-acetylcysteine or taurine-to evaluate the protective effect, if any. Apoptosis was assessed with fluorescence-activated cell sorter flow cytometry. The high-osmolar contrast medium was associated with significantly elevated levels of apoptosis compared with the mannitol control (percentage apoptosis, 27.98 +/- 1.08 vs 6.19 +/- 0.771; p < 0.001). This effect was less pronounced after incubation with the low-osmolar agent but was still significant (percentage apoptosis, 20.19 +/- 0.3665 vs 6.19 +/- 0.771; p < 0.001). The isosmolar agent did not have a significant effect. Both the high- and low-osmolar contrast media coupled with hyperglycemia (30-mmol/L glucose) were associated with a significantly increased level of apoptosis. In all contrast medium groups, taurine had a greater protective effect on attenuation of cell apoptosis than did N-acetylcysteine. The combination of contrast medium and an elevated glucose level has a synergistic effect on apoptosis. Taurine may be a more effective prophylactic antioxidant than the currently advocated antioxidant, N-acetylcysteine.